NDLI: A role for the yeast cell cycle/splicing factor Cdc40 in the G1/S transition

Content Provider	Springer Nature Link
Author	Kaplan, Yosef Kupiec, Martin
Copyright Year	2006
Abstract	The CDC40 (PRP17) gene of S. cerevisiae encodes a splicing factor required for multiple events in the mitotic and meiotic cell cycles, linking splicing with cell cycle control. cdc40 mutants exhibit a delayed G1/S transition, progress slowly through S-phase and arrest at a restrictive temperature in the G2 phase. In addition, they are hypersensitive to genotoxic agents such as methylmethane sulfonate (MMS) and Hydroxyurea (HU). CDC40 has been suggested to control cell cycle through splicing of intron-containing pre-mRNAs that encode proteins important for cell cycle progression. We screened a cDNA overexpression library and isolated cDNAs that specifically suppress the HU/MMS-sensitivity of cdc40 mutants. Most of these cDNAs surprisingly encode chaperones, translation initiation factors and glycolytic enzymes, and none of them is encoded by an intron-containing gene. Interestingly, the cDNAs suppress the G1/S transition delay of cdc40 cells, which is exacerbated by HU, suggesting that cdc40 mutants are HU/MMS-sensitive due to their S-phase entry defect. A role of Cdc40p in passage through G1/S (START) is further supported by the enhanced temperature sensitivity and G1/S transition phenotype of a cdc40 strain lacking the G1 cyclin, Cln2p. We provide evidence that the mechanism of suppression by the isolated cDNAs does not (at least solely) involve up-regulation of the known positive START regulators CLN2, CLN3, DCR2 and GID8, or of the large and small essential ribonucleotide reductase (RNR) subunits, RNR1 and RNR2. Finally, we discuss possible mechanisms of suppression by the cDNAs that imply cell cycle regulation by apparently unrelated processes, such as splicing, translation initiation and glycolysis.
Starting Page	123
Ending Page	140
Page Count	18
File Format	PDF
ISSN	01728083
Journal	Current Genetics
Volume Number	51
Issue Number	2
e-ISSN	14320983
Language	English
Publisher	Springer-Verlag
Publisher Date	2006-12-14
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Cell cycle Hydroxyurea Methylmethane sulfonate Splicing Saccharomyces cerevisiae Proteomics Plant Sciences Cell Biology Biochemistry Microbiology Microbial Genetics and Genomics
Content Type	Text
Resource Type	Article
Subject	Genetics Medicine

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